Pharmaceutical compositions of anisomelic acid and the use thereof
Inventors
Eriksson, John E. • Paul, Preethy • Peuhu, Emilia • Akbarsha, M. A.
Assignees
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Publication Number
US-9345687-B2
Publication Date
2016-05-24
Expiration Date
Abstract
A pharmaceutical composition for anti-viral cancer treatment in mammals, comprising a therapeutically effective amount of Anisomelic acid or salts thereof. The pharmaceutical composition may comprise Anisomelic acid or salt thereof in an oil-in-water emulsion, for example in an isotropic mixture of at least one oil and at least one surfactant or, alternatively, in a hydrophilic solvent and a co-solvents or surfactant or a combination thereof. A method of treating or preventing of cancer in a mammal, wherein the p53 pathway is deregulated by viral oncoproteins, is also provided.
Core Innovation
The invention is a pharmaceutical composition and therapeutic use for anti-viral cancer treatment in mammals using anisomelic acid (AA) or pharmaceutically acceptable salts of anisomelic acid, comprising a therapeutically effective amount of an emulsion of anisomelic acid or salts thereof. The disclosed formulations include an oil-in-water emulsion and emulsions or precursors thereof, including self-microemulsifying drug delivery compositions.
The therapeutic action targets the p53 pathway deregulated by viral oncoproteins E6 and E7. The invention inhibits HPV E6/E7 oncoprotein expression, stabilizes p53 and induces p21-mediated G2/M arrest, and additionally induces p53-independent apoptosis, with down-regulation of cellular inhibitor of apoptosis protein 2 (cIAP2) and intrinsic caspase activation including caspase-9 and caspase-3, together with PARP cleavage.
The invention further addresses formulation and delivery, including an oil-in-water emulsion and precursors capable of forming a fine oil-in-water microemulsion upon agitation and dilution in aqueous media, with optional adjuvants such as antioxidants, co-surfactants, co-solvents, and combinations thereof. The document also describes delivery in a soft or hard gelatin capsule filled with the emulsion, and reports comparative efficacy and tumor suppression using an AA emulsion versus AA alone, together with selectivity toward HPV-positive cervical cancer cells over HPV-negative and non-cancerous cells.
Claims Coverage
The provided content includes five independent claim sets covering pharmaceutical compositions and treatment methods. The main inventive coverage is emulsions of anisomelic acid or salts, including oil-in-water and self-microemulsifying/emulsion precursors, and the stated use in HPV-associated genital disease, non-genital warts, and cancer with p53 pathway deregulated by viral oncoproteins E6 and E7.
Emulsion composition for anti-viral cancer treatment in mammals
A pharmaceutical composition for use in anti-viral cancer treatment in mammals comprising a therapeutically effective amount of an emulsion of anisomelic acid or salts thereof.
HPV-associated genital conditions and non-genital warts treatment
A pharmaceutical composition comprising a therapeutically effective amount of an emulsion of anisomelic acid or salts thereof, for use in treatment of conditions selected from the group consisting of benign or neoplastic genital Human Papilloma Virus associated diseases and non-genital warts.
Oil-in-water emulsion or precursor pharmaceutical composition
A pharmaceutical composition comprising a therapeutically effective amount of anisomelic acid or salt thereof in an oil-in-water emulsion or in a precursor thereof.
Treating cancer with p53 pathway deregulated by E6 and E7
A method of treating cancer or a similar condition in a mammal wherein the p53 pathway is deregulated by viral oncoproteins E6 and E7, comprising administering a therapeutically effective amount of an emulsion of anisomelic acid or salts thereof to said mammal.
Treating benign or neoplastic genital HPV-associated diseases
A method of treating benign or neoplastic genital Human Papilloma Virus associated diseases comprising administering a therapeutically effective amount of an emulsion of anisomelic acid or salts thereof to a mammal in need thereof.
Overall claim coverage centers on pharmaceutical compositions and methods using therapeutically effective emulsions of anisomelic acid or salts, including oil-in-water emulsion or precursors. The use is directed to HPV-associated genital disease and non-genital warts, and to cancer or similar conditions where the p53 pathway is deregulated by viral oncoproteins E6 and E7.
Stated Advantages
Improved apoptosis induction timing with the anisomelic acid emulsion compared with anisomelic acid alone.
Suppression of tumor growth in a CAM model.
Selectivity for HPV-positive cervical cancer cells over HPV-negative and non-cancerous cells.
Documented Applications
Treatment or prevention of cancer or similar conditions associated with viral oncoproteins E6 and E7 and p53 pathway deregulation.
Treatment of benign or neoplastic genital Human Papilloma Virus associated diseases.
Treatment of non-genital warts.
Treatment of cervical cancer.
Treatment of Human Papilloma Virus-mediated cancer.
Use of an anisomelic acid emulsion in a CAM model showing tumor growth suppression.
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